儿童神经母细胞瘤小分子靶向药物研究进展

Research advances in small molecule targeted therapies for pediatric neuroblastoma

关键词:  神经母细胞瘤  高危  生物标志物  靶向治疗  小分子抑制剂

Key words:  neuroblastoma  high-risk  molecular biomarker  targeted therapy  small-molecule inhibitors

摘要:

恶性肿瘤已成为造成儿童死亡的第二大原因,神经母细胞瘤(neuroblastoma,NB)是最常见的儿童恶性实体瘤之一,占儿童癌症死亡率的15%。NB的高度异质性使治疗变得复杂,目前的治疗方法包括手术切除、化疗、干细胞移植、放疗、抗GD2单抗的免疫治疗以及分化诱导剂13-顺式维甲酸治疗等。迫切需要新的治疗方法,改善高危NB的治疗效果,降低复发率,提高患儿生存率。小分子靶向药物具有选择性强、毒副作用低、结构稳定的优点,已被用于多种肿瘤的精准医疗。随着对发病机制的研究,许多分子标志物被发现可作为NB的治疗靶点。综述系统总结了当前NB的潜在靶点以及研究中的小分子靶向药物,以期为儿童NB靶向治疗的进一步发展提供参考。

Abstract:

Malignant tumors have become the second leading cause of death in children, with neuroblastoma (NB) being one of the most common pediatric malignant solid tumors, accounting for 15% of childhood cancer-related mortality. The high heterogeneity exhibited by NB poses challenges to its treatment, which currently encompasses surgical resection, chemotherapy, stem cell transplantation, radiation therapy, anti-GD2 based immunotherapy, and the differentiating agent 13-cis retinoic acid therapy. New therapeutic approaches are urgently needed to enhance the efficacy, reduce recurrence rates, and improve survival rates in high-risk NB children. Small-molecule targeted drugs have the advantages of strong selectivity, low toxicity and stable structure, and have been extensively employed in precision medicine for various tumors. With advancements in understanding the pathogenesis of NB, numerous molecular signatures have been identified as targets for therapeutic intervention. This review provides a comprehensive summary of current potential targets for NB along with ongoing research on small molecule targeted drugs, in order to facilitate further development of targeted therapies in pediatric NB.